scholarly journals Intra-articular Injection of Chitosan-Based Supramolecular Hydrogel for Osteoarthritis Treatment

2021 ◽  
Vol 18 (1) ◽  
pp. 113-125
Author(s):  
Donggang Mou ◽  
Qunying Yu ◽  
Jimei Zhang ◽  
Jianping Zhou ◽  
Xinmin Li ◽  
...  
Keyword(s):  
Hyaluronic Acid ◽  
Cartilage Destruction ◽  
Knee Joints ◽  
Self Healing ◽  
Supramolecular Hydrogel ◽  
Tnf Α ◽  
Osteoarthritis Treatment ◽  
Good Biocompatibility ◽  
In Situ Crosslinking ◽  
And Cartilage

Abstract Background: Pain and cartilage destruction caused by osteoarthritis (OA) is a major challenge in clinical treatment. Traditional intra-articular injection of hyaluronic acid (HA) can relieve the disease, but limited by the difficulty of long-term maintenance of efficacy. Methods: In this study, an injectable and self-healing hydrogel was synthesized by in situ crosslinking of N-carboxyethyl chitosan (N-chitosan), adipic acid dihydrazide (ADH), and hyaluronic acid–aldehyde (HA-ALD). Results: This supramolecular hydrogel sustains good biocompatibility for chondrocytes. Intra-articular injection of this novel hydrogel can significantly alleviate the local inflammation microenvironment in knee joints, through inhibiting the inflammatory cytokines (such as TNF-α, IL-1β, IL-6 and IL-17) in the synovial fluid and cartilage at 2- and even 12-weeks post-injection. Histological and behavioral test indicated that hydrogel injection protected cartilage destruction and relieved pain in OA rats, in comparison to HA injection. Conclusion: This kind of novel hydrogel, which is superior to the traditional HA injection, reveals a great potential for the treatment of OA.

scholarly journals Comparison of Enzymatic Hydrolysis of Polysaccharides from Eggshells Membranes

2016 ◽  
Vol 15 (2) ◽  
pp. 133-141 ◽  
Author(s):  
Eva Ürgeová ◽  
Katarína Vulganová
Keyword(s):  
Extracellular Matrix ◽  
Hyaluronic Acid ◽  
Enzymatic Hydrolysis ◽  
Glucuronic Acid ◽  
Optimal Conditions ◽  
Osteoarthritis Treatment ◽  
Neural Tissues ◽  
Eggshell Membranes ◽  
Hydrolysis Of ◽  
And Cartilage

Abstract AHyaluronic acid (HA) is part of the extracellular matrix of connective, epithelial and neural tissues, as well as the synovial fluid, skin, and cartilage. It is composed of repeating disaccharide units of D-glucuronic acid and N-acetyl glucosamine. Hyaluronic acid is used in abdominal surgery, ophthalmology, dermatology, rhinology; it is usable for the osteoarthritis treatment. The membranes of eggshell are a natural source of hyaluronic acid, collagen, glycosaminoglycan and collagenous proteins. In paper, we tested the possibility of extraction hyaluronic acid from the eggshell membranes by enzymatic hydrolysis. We identified optimal conditions of hydrolysis with trypsin at reaction temperature of 37 °C and pH 8; with pepsin at 40 °C and pH 3, as well as with papain at 60 °C and pH 7.5. The content of hyaluronic acid in samples was determined spectrophotometrically using the carbazole method. The experimental results showed a yield of ~ 4 -4.5 % hyaluronic acid per 1 g of dry eggshell membranes.

scholarly journals Hyaluronic acid synthesis, degradation, and crosslinking in equine osteoarthritis: TNF-α-TSG-6-mediated HC-HA formation

2021 ◽  
Vol 23 (1) ◽  
Author(s):  
Diana C. Fasanello ◽  
Jin Su ◽  
Siyu Deng ◽  
Rose Yin ◽  
Marshall J. Colville ◽  
...  
Keyword(s):  
Gene Expression ◽  
Hyaluronic Acid ◽  
Synovial Fluid ◽  
Complex Formation ◽  
Synovial Membrane ◽  
Fluid Composition ◽  
Fluid Viscosity ◽  
Tnf Α ◽  
Ha Synthase ◽  
And Cartilage

Abstract Background TNF-α-stimulated gene 6 (TSG-6) protein, a TNF-α-responsive hyaladherin, possesses enzymatic activity that can catalyze covalent crosslinks of the polysaccharide hyaluronic acid (HA) to another protein to form heavy chain-hyaluronic acid (HC-HA) complexes in pathological conditions such as osteoarthritis (OA). Here, we examined HA synthase and inflammatory gene expression; synovial fluid HA, TNF-α, and viscosity; and TSG-6-mediated HC-HA complex formation in an equine OA model. The objectives of this study were to (1) evaluate the TNF-α-TSG-6-HC-HA signaling pathway across multiple joint tissues, including synovial membrane, cartilage, and synovial fluid, and (2) determine the impact of OA on synovial fluid composition and biophysical properties. Methods HA and inflammatory cytokine concentrations (TNF-α, IL-1β, CCL2, 3, 5, and 11) were analyzed in synovial fluid from 63 OA and 25 control joints, and HA synthase (HAS1-3), TSG-6, and hyaluronan-degrading enzyme (HYAL2, HEXA) gene expression was measured in synovial membrane and cartilage. HA molecular weight (MW) distributions were determined using agarose gel electrophoresis and solid-state nanopore measurements, and HC-HA complex formation was detected via immunoblotting and immunofluorescence. SEC-MALS was used to evaluate TSG-6-mediated HA crosslinking, and synovial fluid and HA solution viscosities were analyzed using multiple particle-tracking microrheology and microfluidic measurements, respectively. Results TNF-α concentrations were greater in OA synovial fluid, and TSG6 expression was upregulated in OA synovial membrane and cartilage. TSG-6-mediated HC-HA complex formation was greater in OA synovial fluid and tissues than controls, and HC-HA was localized to both synovial membrane and superficial zone chondrocytes in OA joints. SEC-MALS demonstrated macromolecular aggregation of low MW HA in the presence of TSG-6 and inter-α-inhibitor with concurrent increases in viscosity. Conclusions Synovial fluid TNF-α concentrations, synovial membrane and cartilage TSG6 gene expression, and HC-HA complex formation were increased in equine OA. Despite the ability of TSG-6 to induce macromolecular aggregation of low MW HA with resultant increases in the viscosity of low MW HA solutions in vitro, HA concentration was the primary determinant of synovial fluid viscosity rather than HA MW or HC-HA crosslinking. The TNF-α-TSG-6-HC-HA pathway may represent a potential therapeutic target in OA.

scholarly journals Susceptibility of Cyclin-dependent Kinase Inhibitor-1–deficient Mice to Rheumatoid Arthritis From IL-1β–induced Inflammation

2020 ◽  
Author(s):  
Yoshinori Takashima ◽  
Shinya Hayashi ◽  
Koji Fukuda ◽  
Toshihisa Maeda ◽  
Masanori Tsubosaka ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Monoclonal Antibodies ◽  
Kinase Inhibitor ◽  
Joint Inflammation ◽  
Type Ii Collagen ◽  
Cartilage Destruction ◽  
Knee Joints ◽  
Inflammatory Disorder ◽  
Cyclin Dependent Kinase ◽  
And Cartilage

Abstract Background: Rheumatoid arthritis (RA) is a chronic and systemic inflammatory disorder whose progression is modulated by fibroblast-like synoviocytes (FLSs). Cyclin-dependent kinase (CDK) inhibitor 1 (p21) regulates the activation of other CDKs, and we recently reported that p21 deficiency induces susceptibility to osteoarthritis. Here, we focused on joint inflammation to determine the mechanisms associated with p21 function in synovial and cartilage tissues in RA.Methods: p21-knockout (p21-/-) mice and wild-type C57BL/6 (WT p21+/+) mice were used to establish a collagen antibody-induced arthritis (CAIA) model. The severity of arthritis was evaluated visually, and histological and immunohistological analyses performed 7, 14, and 28 days after injection with a cocktail of five monoclonal antibodies that recognize conserved epitopes on various species of type II collagen. The response of p21 siRNA-treated human RA FLSs to IL-1β stimulation was also determined.Results: Arthritis scores were higher in p21-/- mice than those in p21+/+ mice. More severe and prolonged synovitis of the knee joints and earlier loss of staining and cartilage destruction were observed in p21-/- mice than in p21+/+ mice. p21-/- mice expressed higher levels of IL-1β, F4/80, p-IKKα/β, and MMPs in cartilage and synovial tissues at each time point, except for before injection of the monoclonal antibodies, via IL-1β-induced NF-kB signaling. IL-1β stimulation significantly increased MMP expression and enhanced IKKα/β phosphorylation in human FLSs.Conclusion: p21-deficient CAIA mice are susceptible to alterations in the RA phenotype, including joint cartilage destruction and severe synovitis, via IL-1β-induced inflammation. Therefore, p21 regulation may constitute a possible strategy for RA treatment.

scholarly journals Susceptibility of cyclin-dependent kinase inhibitor 1-deficient mice to rheumatoid arthritis arising from interleukin-1β-induced inflammation

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Yoshinori Takashima ◽  
Shinya Hayashi ◽  
Koji Fukuda ◽  
Toshihisa Maeda ◽  
Masanori Tsubosaka ◽  
...  
Keyword(s):  
Kinase Inhibitor ◽  
Cartilage Destruction ◽  
Cyclin Dependent Kinase ◽  
In Vivo Models ◽  
Cyclin Dependent Kinase Inhibitor ◽  
Tnf Α ◽  
Safranin O ◽  
And Cartilage

AbstractWe recently reported that cyclin-dependent kinase inhibitor 1 (p21) deficiency induces osteoarthritis susceptibility. Here, we determined the mechanism underlying the effect of p21 in synovial and cartilage tissues in RA. The knee joints of p21-knockout (p21−/−) (n = 16) and wild type C57BL/6 (p21+/+) mice (n = 16) served as in vivo models of collagen antibody-induced arthritis (CAIA). Arthritis severity was evaluated by immunological and histological analyses. The response of p21 small-interfering RNA (siRNA)-treated human RA FLSs (n = 5 per group) to interleukin (IL)-1β stimulation was determined in vitro. Arthritis scores were higher in p21−/− mice than in p21+/+ mice. More severe synovitis, earlier loss of Safranin-O staining, and cartilage destruction were observed in p21−/− mice compared to p21+/+ mice. p21−/− mice expressed higher levels of IL-1β, TNF-α, F4/80, CD86, p-IKKα/β, and matrix metalloproteinases (MMPs) in cartilage and synovial tissues via IL-1β-induced NF-kB signaling. IL-1β stimulation significantly increased IL-6, IL-8, and MMP expression, and enhanced IKKα/β and IκBα phosphorylation in human FLSs. p21-deficient CAIA mice are susceptible to RA phenotype alterations, including joint cartilage destruction and severe synovitis. Therefore, p21 may have a regulatory role in inflammatory cytokine production including IL-1β, IL-6, and TNF-α.

Suppression of inflammation and cartilage destruction by steroid-rich methanolic extract of Withania Somnifera: A study on collagen induced arthritic rats

2017 ◽  
Vol 2 (2) ◽  
pp. 172
Author(s):  
Mahmood Ahmad Khan ◽  
Mythily Subramaneyaan ◽  
Vinod Kumar Arora ◽  
Rafat Sultana Ahmed
Keyword(s):  
Oxidative Stress ◽  
Inflammatory Cytokines ◽  
Withania Somnifera ◽  
Methanolic Extract ◽  
Bone Erosion ◽  
Cartilage Destruction ◽  
Normal Serum ◽  
Inflammatory Disorder ◽  
Tnf Α ◽  
And Cartilage

Rheumatoid arthritis (RA) is an inflammatory disorder characterized by oxidative stress, inflammation and cartilage destruction. Withania somnifera (WS) is used in Indian folk medicine for the treatment of various musculoskeletal disorders. WS is considered to possess potent antioxidant and anti-inflammatory activities. The aim of the present study was to evaluate the possible mechanism of action of methanolic extract of Withania somnifera roots (WSMe) against collagen induced arthritic (CIA) rats. Arthritis in rats was induced by subcutaneous injection of bovine type II collagen and was treated with WSMe at the dose of 200 mg/kg BW for 20 days after arthritis was induced. Number of biochemical, molecular and histological changes was observed in CIA rats. In CIA rats we found an imbalance in antioxidant and oxidant status as level of MDA was increased while GST, GSH and FRAP was found to be decreased. Administration of WSMe200 significantly ameliorates the level of antioxidant and oxidant to near normal. Serum concentration of transcription factor NF-kB, inflammatory cytokines like TNF-α, IL-1β, IL-6 and IL-10 were altered in CIA rats. In consistent to this mRNA expression of NF-kB, TNF-α and MMP-8 were also found to be Up-regulated, which were significantly inhibited by WSMe200 treatment. These findings are positively correlated with the results of histological examinations of joints, which showed reduced inflammation and bone erosion in the treated group. The ability to inhibit the production of oxidative stress and subsequent modulation of the inflammatory cytokines shows the protective effect of WSMe and its potential use for the treatment of arthritis.

scholarly journals Appearance of calpain correlates with arthritis and cartilage destruction in collagen induced arthritic knee joints of mice.

1995 ◽  
Vol 54 (6) ◽  
pp. 477-483 ◽  
Author(s):  
Z Szomor ◽  
K Shimizu ◽  
Y Fujimori ◽  
S Yamamoto ◽  
T Yamamuro
Keyword(s):  
Cartilage Destruction ◽  
Knee Joints ◽  
And Cartilage ◽  
Arthritic Knee

scholarly journals Biomimetic nanotherapy: core–shell structured nanocomplexes based on the neutrophil membrane for targeted therapy of lymphoma

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Qiangqiang Zhao ◽  
Duanfeng Jiang ◽  
Xiaoying Sun ◽  
Qiuyu Mo ◽  
Shaobin Chen ◽  
...  
Keyword(s):  
Mesoporous Silica Nanoparticles ◽  
Treatment Options ◽  
Inflammatory Factors ◽  
Main Method ◽  
Tnf Α ◽  
Good Biocompatibility ◽  
Inflammatory Drugs ◽  
Anti Inflammatory ◽  
New Treatment ◽  
Lymphoma Therapy

Abstract Background Non-Hodgkin’s lymphoma (NHL) is a malignant disease of lymphoid tissue. At present, chemotherapy is still the main method for the treatment of NHL. R-CHOP can significantly improve the survival rate of patients. Unfortunately, DOX is the main cytotoxic drug in R-CHOP and it can lead to adverse reactions. Therefore, it is particularly important to uncover new treatment options for NHL. Results In this study, a novel anti-tumor nanoparticle complex Nm@MSNs-DOX/SM was designed and constructed in this study. Mesoporous silica nanoparticles (MSNs) loaded with Doxorubicin (DOX) and anti-inflammatory drugs Shanzhiside methylester (SM) were used as the core of nanoparticles. Neutrophil membrane (Nm) can be coated with multiple nanonuclei as a shell. DOX combined with SM can enhance the anti-tumor effect, and induce apoptosis of lymphoma cells and inhibit the expression of inflammatory factors related to tumorigenesis depending on the regulation of Bcl-2 family-mediated mitochondrial pathways, such as TNF-α and IL-1β. Consequently, the tumor microenvironment (TME) was reshaped, and the anti-tumor effect of DOX was amplified. Besides, Nm has good biocompatibility and can enhance the EPR effect of Nm@MSNs-DOX/SM and increase the effect of active targeting tumors. Conclusions This suggests that the Nm-modified drug delivery system Nm@MSNs-DOX/SM is a promising targeted chemotherapy and anti-inflammatory therapy nanocomplex, and may be employed as a specific and efficient anti-Lymphoma therapy.

scholarly journals Hyaluronic Acid-Modified and TPCA-1-Loaded Gold Nanocages Alleviate Inflammation

Pharmaceutics ◽  
2019 ◽  
Vol 11 (3) ◽  
pp. 143 ◽  
Author(s):  
Jingnan Zhao
Keyword(s):  
Hyaluronic Acid ◽  
Inflammatory Cells ◽  
Oxygen Species ◽  
Necrosis Factor Alpha ◽  
Tnf Α ◽  
Nanogold Particles ◽  
Gold Nanocages ◽  
Factor Alpha ◽  
Anti Inflammatory ◽  
Necrosis Factor

Gold nanocages (AuNCs) are biocompatible and porous nanogold particles that have been widely used in biomedical fields. In this study, hyaluronic acid (HA) and peptide- modified gold nanocages (HA-AuNCs/T/P) loaded with 2-[(aminocarbonyl)amino]-5-(4-fluorophenyl)-3-thiophenecarboxamide (TPCA-1) were prepared to investigate their potential for combating inflammation. TPCA-1 was released from AuNCs, intracellularly when HA was hydrolyzed by hyaluronidase. HA-AuNCs/T/P show a much higher intracellular uptake than AuNCs/T/P, and exhibit a much higher efficacy on the suppression of tumor necrosis factor alpha (TNF-α) and interleukin 6 (IL-6) than free TPCA-1, suggesting great improvement to the anti-inflammatory efficacy of TPCA-1 through the application of AuNCs. HA-AuNCs/T/P can also reduce the production of reactive oxygen species in inflammatory cells. This study suggests that HA-AuNCs/T/P may be potential agents for anti-inflammatory treatment, and are worthy of further investigation.

Sign in / Sign up

Export Citation Format

Share Document